The goal of the proposed research is to elucidate the role monoamines play in tolerance to and physical dependence on ethanol. Toward this end, we plan to continue our examination of the mechanisms by which ethanol interacts with central and peripheral monoaminergic (dopaminergic, noradrenergic, serotonergic) neurons. The underlying mechanisms by which acute or chronic ethanol treatment affects the turnover of monoamines will be investigated. Possible mediation of the effects of ethanol by other neuronal inputs will be examined, as well as the possible influence of basal neuronal activity. Secondly, the involvement of monoamines in both tolerance and dependence will be investigated. Rates of development and decay of tolerance and dependence will be determined and correlated with neurochemical changes produced by ethanol.